Susan M. Fischer, Ph.D.
Professor, Carcinogenesis
The University of Texas M. D. Anderson Cancer Center
Leader Research Focus Area 3
smfischer@mdanderson.org
Education
High Point College, High Point, NC, BS, 1969, Biology
University of Wyoming, Laramie, WY, MS, 1971, Physiology
University of Wyoming, Laramie, WY, PHD, 1974, Physiology
Research Interests
- Skin carcinogenesis
- Pancreatic cancer
- Inflammation
- Arachidonic acid metabolism
- Prostaglandins
The primary focus of my laboratory is to elucidate the role of inflammatory processes in the tumor-promotion stage of carcinogenesis. The emphasis of this work is on mediators of inflammation, including the prostaglandin metabolites of arachidonic acid, cytokines, and growth factors. Studies currently underway are concerned with understanding the specific roles prostaglandin E2 (PGE2) in the development of cancer. We previously showed that overexpression of the enzyme, cyclooxygenase-2 (COX-2), that synthesizes PGE2 confers tumor promoting activity in initiated mouse skin. This indicates that at high levels PGE2 is an endogenous tumor promoter and may be the mechanism by which phorbol esters and UV light, which are known to induce COX-2, function as tumor promoters. To determine the pathophysiological role of PGE2 in carcinogenesis, we are investigating the role of the four EP membrane receptors for PGE2, using knockout and over-expressing mice. We showed that the EP2 receptor contributes to tumor promotion, likely via its ability to upregulate VEGF, cyclin D1 and other genes known to be important to cancer development. Ongoing studies on the EP1 and EP4 receptors suggest that these mice are self-promoting, i.e., no exogenous tumor promoters are required for tumor development following initiation. Current projects are focused on trying to understand the molecular mechanisms by which this occurs, i.e., what signaling pathways are activated by PGE2 and which receptors transduce the tumor-promoting signals. This information should be useful in designing new approaches to chemoprevention/intervention in skin cancer development. One of our transgenic mice (K5.COX-2) develops spontaneous pancreatitis that progresses to pancreatic ductal adenocarcinoma with a 100% penetrance. Current studies are focused on elucidating the mechanisms involved, particularly with regard to the soluble and inflammatory inflammatory components. Additional studies are investigating the effect of obesity-inducing vs calorie-restricted diets on the development of lesions in this model. Studies in progress indicate that energy balance has a strong effect on the development and progression of this disease, in that calorie restriction significantly protects against disease progression. Ongoing work indicates that IGF-1 levels may mediate this effect, i.e., obesity increases circulating IGF-1, calorie restriction reduces it, and genetic reduction of IGF-1 reduces the growth of xenografts of pancreatic cancer cell lines. The relationship between IGF-1 and inflammatory cytokines is currently being explored.